This proposed research focuses on the advanced development and validation of an innovative, extensible diagnostics platform to markedly improve early cancer detection and cancer risk assessment through the ultrasensitive readout of biomarker panels. The creation of a surface-enhanced Raman scattering (SERS) immunoassay diagnostic platform, realized by coupling sensitive SERS detection with nanoparticle labels, enhanced analyte delivery, and immunoassay architectures, will result in a simple platform capable of multiplexed biomarker detection. This intelligent use of a panel of biomarkers will serve as the cornerstone in making subclinical cancer detection a reality. Integral to this work is the use of pancreatic adenocarcinoma (PA) as a disease model to validate the platform. PA exhibits traits common to most diseases that progress asymptomatically, including the unavailability of one ideal tumor marker with high clinical sensitivity and specificity. Since development of PA arises from a range of causative mutations in individuals, a panel of multiple biomarkers with overlapping detection capabilities is likely to provide improved accuracy. Assembly of such a panel from markers that have demonstrated limited correlative value individually provides a vehicle to assess the figures of merit and multiplexing ability of the SERS platform. Currently, our ability to identify health risk, disease susceptibility, and response to therapy remains unreachable due in part to our technical inability to easily screen a single sample for the large number of biomarkers that potentially make up a "disease map" and to do so at costs that enable routine testing for everyone. The SERS platform is designed to remove this hurdle. Once validated, the platform could also be used for marker and marker panel discovery and is uniquely suited for rapid deployment as a cost-effective, portable, and robust system for multiplexed diagnostic assays in a clinical setting or to form an essential part of the personalized medicine infrastructure. PUBLIC HEALTH RELEVANCE: This proposal seeks to make early cancer detection and the associated promise of improved outcomes accessible to the general public. Current technical limitations have hindered the ability to rapidly screen large numbers of biomarkers from individual patients, a method purported to have improved diagnostic, prognostic, and therapeutic efficacy over a single biomarker. The project proposes developing a platform that uses a rapid, cost-effective optical detection technology to simultaneously measure hundreds of biomarkers in a single drop of blood.